title: Population pharmacokinetics of doxycycline in the tears and plasma of northern elephant seals (Mirounga angustirostris) following oral drug administration.
abstract: OBJECTIVE
  To assess tear and plasma concentrations of doxycycline following oral administration to northern elephant seals (Mirounga angustirostris).
  
  
  METHODS
  Pharmacokinetic study.
  
  
  METHODS
  18 juvenile northern elephant seals without signs of ocular disease.
  
  
  METHODS
  Study seals were receiving no medications other than a multivitamin and were free from signs of ocular disease as assessed by an ophthalmic examination. Doxycycline (10 or 20 mg/kg [4.5 or 9.1 mg/lb]) was administered orally every 24 hours for 4 days. Tear and plasma samples were collected at fixed time points, and doxycycline concentration was assessed by means of liquid chromatography-tandem mass spectrometry. Concentration-time data were calculated via noncompartmental analysis.
  
  
  RESULTS
  Following administration of doxycycline (10 mg/kg/d, PO), maximum plasma doxycycline concentration was 2.2 μg/mL at 6.1 hours on day 1 and was 1.5 μg/mL at 4.0 hours on day 4. Administration of doxycycline (20 mg/kg/d, PO) produced a maximum plasma doxycycline concentration of 2.4 μg/mL at 2.3 hours on day 1 and 1.9 μg/mL at 5.8 hours on day 4. Doxycycline elimination half-life on day 4 in animals receiving doxycycline at a dosage of 10 or 20 mg/kg/d was 6.7 or 5.6 hours, respectively. Mean plasma-to-tear doxycycline concentration ratios over all days were not significantly different between the low-dose (9.85) and high-dose (9.83) groups. For both groups, doxycycline was detectable in tears for at least 6 days following cessation of dosing.
  
  
  CONCLUSIONS
  Oral administration of doxycycline at the doses tested in the present study resulted in concentrations in the plasma and tears of northern elephant seals likely to be clinically effective for treatment of selected cases of systemic infectious disease, bacterial ulcerative keratitis, and ocular surface inflammation. This route of administration should be considered for treatment of corneal disease in northern elephant seals and possibly other related pinniped species.
authors.affiliation: Veterinary Medical Teaching Hospital, School of Veterinary Medicine, University of California-Davis, Davis, CA 95616.
authors.forename: Kate S
authors.initials: KS
authors.lastname: Freeman
authors.forename: Sara M
authors.initials: SM
authors.lastname: Thomasy
authors.forename: Scott D
authors.initials: SD
authors.lastname: Stanley
authors.forename: William
authors.initials: W
authors.lastname: Van Bonn
authors.forename: Frances
authors.initials: F
authors.lastname: Gulland
authors.forename: Ari S
authors.initials: AS
authors.lastname: Friedlaender
authors.forename: David J
authors.initials: DJ
authors.lastname: Maggs
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics*; D019540:Area Under Curve; D004318:Doxycycline / Q000008:administration & dosage / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics*; D005260:Female; D006207:Half-Life; D008297:Male; D046048:Seals, Earless / Q000097:blood*; D013666:Tears / Q000737:chemistry*
chemical_list: D000900:Anti-Bacterial Agents; D004318:Doxycycline